Sex Differences in Outcomes of Percutaneous Pulmonary Artery Thrombectomy in Patients With Pulmonary Embolism.

BACKGROUND: The sex differences in use, safety outcomes, and health-care resource use of patients with pulmonary embolism (PE) undergoing percutaneous pulmonary artery thrombectomy are not well characterized. RESEARCH QUESTION: What are the sex differences in outcomes for patients diagnosed with PE who undergo percutaneous pulmonary artery thrombectomy? STUDY DESIGN AND METHODS: This retrospective cross-sectional study used national inpatient claims data to identify patients in the United States with a discharge diagnosis of PE who underwent percutaneous thrombectomy between January 2016 and December 2018. We evaluated the demographics, comorbidities, safety outcomes (in-hospital mortality), and health-care resource use (discharge to home, length of stay, and hospital charges) of patients with PE undergoing percutaneous thrombectomy. RESULTS: Among 1,128,904 patients with a diagnosis of PE between 2016 and 2018, 5,160 patients (0.5%) underwent percutaneous pulmonary artery thrombectomy. When compared with male patients, female patients showed higher procedural bleeding (16.9% vs 11.2%; P < .05), required more blood transfusions (11.9% vs 5.7%; P < .05), and experienced more vascular complications (5.0% vs 1.5%; P < .05). Women experienced higher in-hospital mortality (16.9% vs 9.3%; adjusted OR, 1.9; 95% CI, 1.2-3.0; P = .003) when compared with men. Although length of stay and hospital charges were similar to those of men, women were less likely to be discharged home after surviving hospitalization (47.9% vs 60.3%; adjusted OR, 0.7; 95% CI, 0.50-0.99; P = .04). INTERPRETATION: In this large nationwide cohort, women with PE who underwent percutaneous thrombectomy showed higher morbidity and in-hospital mortality compared with men.

Reduced admission rates and resource utilization for chest pain patients using an electronic health record-embedded clinical pathway in the emergency department.

OBJECTIVES: Assess the impact of an electronic health record (EHR)-embedded clinical pathway (ePATH) as compared to a paper-based clinical decision support tool on outcomes for patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS). METHODS: A retrospective, quasi-experimental study using difference-in-differences and interrupted time series specifications to evaluate the impact of an EHR-embedded clinical pathway between April 2013 and July 2017. The intervention was implemented in February 2016 at a large academic tertiary hospital and compared to a local community hospital without the intervention. Eligible patients included adults (>18 years) presenting to the ED with chest pain who had a troponin ordered within 2 hours of arrival and a chest pain-related diagnosis. Patients with initial evidence of acute myocardial infarction were excluded. Primary outcomes included rates of admission and stress testing, hospital length of stay, and occurrence of major adverse cardiac events. RESULTS: On average, there were 170 chest pain visits per month at the intervention site. The frequency of hospital admission (unadjusted 28.2% to 20.9%, P < 0.001) and stress testing (unadjusted 15.8% to 12.7%, P < 0.001) significantly declined after ePATH implementation. After comparison with the comparator site, ePATH was still associated with a significant reduction in hospital admissions (-10.79%, P < 0.001) and stress testing (-6.05%, P < 0.001). Hospital length of stay and rates of major adverse cardiac events did not significantly change. CONCLUSIONS: Implementation of ePATH for patients presenting to the ED with chest pain was associated with safe reductions in hospital admission and stress testing. ePATH appears to be an effective tool for implementing evidence-based guidelines for ED patients with chest pain.

Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac Fibrosis.

BACKGROUND: Genetic diversity and the heterogeneous nature of cardiac fibroblasts (CFbs) have hindered characterization of the molecular mechanisms that regulate cardiac fibrosis. The Hybrid Mouse Diversity Panel offers a valuable tool to examine genetically diverse cardiac fibroblasts and their role in fibrosis. METHODS: Three strains of mice (C57BL/6J, C3H/HeJ, and KK/HlJ) were selected from the Hybrid Mouse Diversity Panel and treated with either isoproterenol (ISO) or saline by an intraperitoneally implanted osmotic pump. After 21 days, cardiac function and levels of fibrosis were measured by echocardiography and trichrome staining, respectively. Activation and proliferation of CFbs were measured by in vitro and in vivo assays under normal and injury conditions. RNA sequencing was done on isolated CFbs from each strain. Results were analyzed by Ingenuity Pathway Analysis and validated by reverse transcription-qPCR, immunohistochemistry, and ELISA. RESULTS: ISO treatment in C57BL/6J, C3H/HeJ, and KK/HlJ mice resulted in minimal, moderate, and extensive levels of fibrosis, respectively (n=7-8 hearts per condition). Isolated CFbs treated with ISO exhibited strain-specific increases in the levels of activation but showed comparable levels of proliferation. Similar results were found in vivo, with fibroblast activation, and not proliferation, correlating with the differential levels of cardiac fibrosis after ISO treatment. RNA sequencing revealed that CFbs from each strain exhibit unique gene expression changes in response to ISO. We identified Ltbp2 as a commonly upregulated gene after ISO treatment. Expression of LTBP2 was elevated and specifically localized in the fibrotic regions of the myocardium after injury in mice and in human heart failure patients. CONCLUSIONS: This study highlights the importance of genetic variation in cardiac fibrosis by using multiple inbred mouse strains to characterize CFbs and their response to ISO treatment. Our data suggest that, although fibroblast activation is a response that parallels the extent of scar formation, proliferation may not necessarily correlate with levels of fibrosis. In addition, by comparing CFbs from multiple strains, we identified pathways as potential therapeutic targets and LTBP2 as a marker for fibrosis, with relevance to patients with underlying myocardial fibrosis.

Extensive volatile loss during formation and differentiation of the Moon.

Low estimated lunar volatile contents, compared with Earth, are a fundamental observation for Earth-Moon system formation and lunar evolution. Here we present zinc isotope and abundance data for lunar crustal rocks to constrain the abundance of volatiles during the final stages of lunar differentiation. We find that ferroan anorthosites are isotopically heterogeneous, with some samples exhibiting high δ(66)Zn, along with alkali and magnesian suite samples. Since the plutonic samples were formed in the lunar crust, they were not subjected to degassing into vacuum. Instead, their compositions are consistent with enrichment of the silicate portions of the Moon in the heavier Zn isotopes. Because of the difference in δ(66)Zn between bulk silicate Earth and lunar basalts and crustal rocks, the volatile loss likely occurred in two stages: during the proto-lunar disk stage, where a fraction of lunar volatiles accreted onto Earth, and from degassing of a differentiating lunar magma ocean, implying the possibility of isolated, volatile-rich regions in the Moon's interior.

Comparison of PECARN, CATCH, and CHALICE rules for children with minor head injury: a prospective cohort study.

STUDY OBJECTIVE: We evaluate the diagnostic accuracy of clinical decision rules and physician judgment for identifying clinically important traumatic brain injuries in children with minor head injuries presenting to the emergency department. METHODS: We prospectively enrolled children younger than 18 years and with minor head injury (Glasgow Coma Scale score 13 to 15), presenting within 24 hours of their injuries. We assessed the ability of 3 clinical decision rules (Canadian Assessment of Tomography for Childhood Head Injury [CATCH], Children's Head Injury Algorithm for the Prediction of Important Clinical Events [CHALICE], and Pediatric Emergency Care Applied Research Network [PECARN]) and 2 measures of physician judgment (estimated of <1% risk of traumatic brain injury and actual computed tomography ordering practice) to predict clinically important traumatic brain injury, as defined by death from traumatic brain injury, need for neurosurgery, intubation greater than 24 hours for traumatic brain injury, or hospital admission greater than 2 nights for traumatic brain injury. RESULTS: Among the 1,009 children, 21 (2%; 95% confidence interval [CI] 1% to 3%) had clinically important traumatic brain injuries. Only physician practice and PECARN identified all clinically important traumatic brain injuries, with ranked sensitivities as follows: physician practice and PECARN each 100% (95% CI 84% to 100%), physician estimates 95% (95% CI 76% to 100%), CATCH 91% (95% CI 70% to 99%), and CHALICE 84% (95% CI 60% to 97%). Ranked specificities were as follows: CHALICE 85% (95% CI 82% to 87%), physician estimates 68% (95% CI 65% to 71%), PECARN 62% (95% CI 59% to 66%), physician practice 50% (95% CI 47% to 53%), and CATCH 44% (95% CI 41% to 47%). CONCLUSION: Of the 5 modalities studied, only physician practice and PECARN identified all clinically important traumatic brain injuries, with PECARN being slightly more specific. CHALICE was incompletely sensitive but the most specific of all rules. CATCH was incompletely sensitive and had the poorest specificity of all modalities.

Orbital invasion by ACTH-secreting pituitary adenomas.

Orbital invasion by pituitary tumors is rare. To the best of the authors' knowledge, adrenocorticotrophin (ACTH)-secreting pituitary tumors with orbital invasion have not been described in MEDLINE indexed literature. The authors report 2 cases of ACTH-secreting tumors with orbital invasion. One patient had a history of endoscopic transsphenoidal subtotal resection of an ACTH-secreting tumor and presented with recurrence in the orbit. The second patient had a long history of visual loss considered to be secondary to glaucoma. Neuroimaging revealed a destructive mass involving the sella turcica with extension in the right orbit. Debulking of the mass was performed via a transsphenoidal approach, and histopathology revealed an ACTH-secreting adenoma. ACTH-secreting adenoma should be considered in the differential of tumors involving the sella turcica with orbital invasion.

Student perspectives on the diversity climate at a U.S. medical school: the need for a broader definition of diversity.

BACKGROUND: Medical schools frequently experience challenges related to diversity and inclusiveness. The authors conducted this study to assess, from a student body's perspective, the climate at one medical school with respect to diversity, inclusiveness and cross-cultural understanding. METHODS: In 2008 students in the doctor of medicine (MD), physical therapy (PT) and physician assistant programs at a public medical school were asked to complete a diversity climate survey consisting of 24 Likert-scale, short-answer and open-ended questions. Questions were designed to measure student experiences and attitudes in three domains: the general diversity environment and culture; witnessed negative speech or behaviors; and diversity and the learning environment. Students were also asked to comment on the effectiveness of strategies aimed at promoting diversity, including diversity and sensitivity training, pipeline programs, student scholarships and other interventions. Survey responses were summarized using proportions and 95 percent confidence intervals (95% CI), as well as inductive content analysis. RESULTS: Of 852 eligible students, 261 (31%) participated in the survey. Most participants agreed that the school of medicine (SOM) campus is friendly (90%, 95% CI 86 to 93) and welcoming to minority groups (82%, 95% CI 77 to 86). Ninety percent (95% CI 86 to 93) found educational value in a diverse faculty and student body. However, only 37 percent (95% CI 30 to 42) believed the medical school is diverse. Many survey participants reported they have witnessed other students or residents make disparaging remarks or exhibit offensive behaviors toward minority groups, most often targeting persons with strong religious beliefs (43%, 95% CI 37 to 49), low socioeconomic status (35%, 95% CI 28 to 40), non-English speakers (34%, 95% CI 28 to 40), women (30%, 95% CI 25 to 36), racial or ethnic minorities (28%, 95% CI 23 to 34), or gay, lesbian, bisexual or transgendered (GLBT) individuals (25%, 95% CI 20 to 30). Students witnessed similar disparaging or offensive behavior by faculty members toward persons with strong religious beliefs (18%, 95% CI 14 to 24), persons of low socioeconomic status (12%, 95% CI 9 to 17), non-English speakers (10%, 95% CI 6 to 14), women (18%, 95% CI 14 to 24), racial or ethnic minorities (12%, 95% CI 8 to 16) and GLBT individuals (7%, 95% CI 4 to 11). Students' open-ended comments reinforced the finding that persons holding strong religious beliefs or conservative values were the most common targets of disparaging or offensive behavior. CONCLUSIONS: These data suggest that medical students believe that diversity and a climate of inclusiveness and respect are important to a medical school's educational and clinical care missions. However, according to these students, the institution must embrace a broader definition of diversity, such that all minority groups are valued, including individuals with conservative viewpoints or strong religious beliefs, the poor and uninsured, GLBT individuals, women and non-English speakers.

Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas.

PURPOSE: The purpose of this study was to evaluate morphological changes induced by corneal collagen cross-linking in a human ex vivo cornea, using confocal, electron, and light microscopy. METHODS: The central epithelium was partially removed from ex vivo human corneal buttons. Riboflavin 0.1% solution was applied before ultraviolet A light treatment and then for every 2 minutes for 30 minutes while the corneas were exposed to ultraviolet A light at a wavelength of 370 nm and intensity of 3 mW/cm(2). Each cornea was evaluated using confocal, electron, and light microscopy. RESULTS: Confocal microscopy demonstrated normal-appearing corneas on their initial pretreatment examination, with reduced stromal detail. After treatment, a superficial layer of highly reflective spherical structures (4-10 microm) was observed. Many of these hyperreflective structures appeared up to a depth of 300 microm. The remainder of the corneal stroma and endothelium appeared normal. Electron microscopy showed keratocyte apoptotic changes to a depth of 300 microm. No observable pathologic changes were seen on histology. CONCLUSIONS: Based on clinical studies, corneal cross-linking is a promising treatment that appears to be safe and to halt ectatic corneal disease progression. Initial European studies used animal models to extrapolate human protocols. In conjunction with clinical studies, we believe that human ex vivo corneal studies provide a means to evaluate the structural and morphological changes associated with this procedure, within human corneas, in a manner that cannot be accomplished in vivo.

Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty.

PURPOSE: To evaluate the long-term efficacy and side effects of off-label topical tacrolimus 0.03% ointment (Protopic; Fujisawa Health, Deerfield, IL) as a sole second-line immunosuppressive agent in the management of high-risk corneal grafts. METHODS: Four consecutive patients underwent high-risk penetrating keratoplasty (4 grafts) with a prior diagnosis of corneal scar secondary to herpetic keratitis, keratoconus, acanthamoeba keratitis, and Fuchs endothelial dystrophy, respectively. All 4 patients developed steroid-induced glaucoma and failed traditional immunosuppressant therapy. Patients were started on topical tacrolimus ointment 0.03%, twice daily, which was tapered to the lowest possible therapeutic dose that maintained its antirejection efficacy. Patients were monitored for adverse treatment effects. The mean follow-up was 33 months (range, 26-48 months), and the mean treatment duration was 22.6 months (range, 13-32 months). RESULTS: All 4 high-risk corneal transplant patients experienced episodes of acute rejection that was successfully reversed with topical tacrolimus treatment. During tacrolimus treatment, there were no further episodes of graft rejection and no incidents of herpes simplex virus infection or reactivation, with the longest follow-up being 4 years. Two patients have been successfully tapered off tacrolimus, and 2 patients are currently on once-daily dosing. No adverse effects were observed. CONCLUSIONS: Topical tacrolimus 0.03% ointment seems to be a promising second-line immunosuppressant in management of high-risk grafts.

Current applications of clinical confocal microscopy.

PURPOSE OF REVIEW: Confocal microscopy's role within ophthalmology has been evolving since the introduction of this technology in 1955. The purpose of this review is to describe the confocal microscope and illustrate its recent ophthalmic applications. RECENT FINDINGS: Numerous investigators have used confocal microscopy to research ophthalmic disease and to find new diagnostic applications. This review will describe the development and uses of this technology. The cornea was the first ophthalmic tissue to be imaged due to its transparency, although, tissues, such as conjunctiva, are now being studied. This article will review normal confocal corneal appearance and discuss a wide range of recent applications that include corneal infections, dystrophies and disease. Furthermore, this article will discuss recent developments in refractive surgery, ocular surgery and various miscellaneous discoveries. SUMMARY: Confocal microscopy is developing into a powerful research and diagnostic tool in ophthalmology. The future uses of this novel technology will evolve and is increasingly becoming a vital tool in the ophthalmologist's armamentarium.

A robust small-molecule microarray platform for screening cell lysates.

Herein we report the expanded functional group compatibility of small-molecule microarrays to include immobilization of primary alcohols, secondary alcohols, phenols, carboxylic acids, hydroxamic acids, thiols, and amines on a single slide surface. Small-molecule "diversity microarrays" containing nearly 10,000 known bioactive small molecules, natural products, and small molecules originating from several diversity-oriented syntheses were produced by using an isocyanate-mediated covalent capture strategy. Selected printed bioactive compounds were detected with antibodies against compounds of interest. The new surface of the diversity microarrays is highly compatible with approaches involving cellular lysates. This feature has enabled a robust, optimized screening methodology using cellular lysates, allowing the detection of specific interactions with a broad range of binding affinity by using epitope-tagged or chimeric fluorescent proteins without prior purification. We believe that this expanded research capability has considerable promise in biology and medicine.